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Biomedical subjects

H Naganuma

Publications and source records attributed to H Naganuma.

At least 19 recordsLinked to original sources

A mechanism of resistance to TRAIL/Apo2L-induced apoptosis of newly established glioma cell line and sensitisation to TRAIL by genotoxic agents.

Most tumour cells are sensitive to TRAIL-induced apoptosis, but not normal cells; thus, cancer therapy using TRAIL is expected clinically. Several tumour cells are resistant to TRAIL-induced apoptosis, and various mechanisms of such resistance were reported in individual cases. In this study, we established a TRAIL-resistant glioma cell line, which completely lacked TRAIL receptors. In addition, this tumour cell line had wild-type p53 tumour-suppressive gene, suggesting new mechanisms for tumour cells to expand and escape from immune surveillance. The present study further explored the mechanisms that determine the sensitivity to TRAIL. We show that genotoxic agents such as cisplatin, doxorubicin and camptothecin, in addition to UV radiation, can induce TRAIL-R2 on the cell surface of TRAIL receptor-negative tumour cells. Newly synthesised TRAIL-R2 is functional, so apoptosis is effectively induced by TRAIL, but it is significantly inhibited by constitutive expression of dominant-negative p53. In addition, apoptosis induced by pretreatment of genotoxic agents and additional stimulation of TRAIL is efficiently inhibited by either antagonistic anti-TRAIL-R2 antibody or pan-caspase inhibitor z-VAD-FMK. Taken together, these findings suggest that resistance to TRAIL by lack of TRAIL receptors on glioma is restored by genotoxic agents, which support the new strategies for tumour killing by TRAIL-bearing cytotoxic cells in combination with genotoxic treatment.

Antineoplastic Agents↗

[Transportation for a pediatric heart transplant candidate to Germany].

A 8-year-old girl who underwent a total cavopulmonary connection as an one-staged repair for tricuspid atresia (Ic) had had a progressive dilated cardiomyopathy. Despite of any medical support, her left ventricular ejection fraction had been ranged from 10% to 20% since 4 months after Fontan operation. This patient was decided to apply for a heart transplantation in Germany 17 months after Fontan operation. An administration of the sufficient amount of inotropics and oxygen, volume resuscitation, reduction of the peripheral circulation at the time of take-off, and a meticulous monitoring may contribute to the successful transportation of the critically ill patient.

Cardiomyopathy, Dilated↗

Mesenteric lipoma: report of a case with emphasis on US findings.

Mesenteric lipoma (ML) is a relatively rare disease that has been very infrequently reported. We present the clinical data and medical imaging results of an asymptomatic case with ML incidentally detected by sonography (US). On US the lesion was imaged as a well-demarcated hypoechoic mass with multiple linear echoes. The mass also changed location under probe compression. The lesion was imaged as a clearly demarcated non-enhanced homogeneous fat-density mass on CT. Color Doppler US and angiography confirmed the avascular nature of the mass. Knowledge of the US findings in this case is useful for the diagnosis of ML.

Adult↗

Antisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cells.

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-beta. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisense-transfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a dose-related manner. Maximum inhibition of migration was achieved by 100 microg/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells.

Blotting, Western↗

Atrioventricular groove patch plasty for anatomically corrected malposition of the great arteries.

OBJECTIVE: In anatomically corrected malposition of the great arteries, dextroposition of the posterior pulmonary artery and levoposition of the anterior aorta are associated with the leftward deviation of the proximal portion of the right coronary artery away from the right atrioventricular groove. This anatomic feature allows a transannular subpulmonary patch plasty of the right ventricular outflow tract along the right atrioventricular groove between the right coronary artery and the tricuspid anterior anulus (ie, atrioventricular groove patch plasty) for relief of subpulmonary stenosis without jeopardizing the right coronary artery. METHODS: This report describes the midterm results of a new surgical technique, atrioventricular groove patch plasty with a monocuspid transannular patch for subpulmonary stenosis, in 3 patients with anatomically corrected malposition of the great arteries, along with a concomitant closure of ventricular septal defects. RESULTS: Postoperative catheterization revealed adequate relief of pulmonary stenosis, with a pressure gradient of 8.0 +/- 3.5 mm Hg and with normalized right ventricular pressure (33 +/- 10 mm Hg), contributing to excellent midterm results with no late death and reoperation during a postoperative follow-up period of 70 +/- 47 months. CONCLUSION: This technique provides a promising alternative to Rastelli-type conduit repair for subpulmonary stenosis in anatomically corrected malposition of the great arteries.

Cardiac Catheterization↗

Three-dimensional analysis of morphological aspects of the human saccular macula.

The 3-dimensional shape of the human saccular macula and its orientation in the skull were quantitated in this study. The semicircular canals and saccular maculae were reconstructed 3-dimensionally on a computer from 3 human temporal bones. The 380 to 522 triangles in the entire area of the saccular macula were made by drawing lines between 2 adjacent points every 100-pm width of the saccular macula in each section. The angles between each triangle and each estimated standard axis in the skull obtained were calculated. This information will provide standard data regarding the 3-dimensional morphological aspects of the saccular macula for further investigations of the function of the sacculus. It was determined that the 3-dimensional shape of the saccular macula was not a plane, but was a curved surface like that of an ellipsoid. It is thought that this shape is necessary in order for the saccular macula to detect wide-range linear acceleration.

Acoustic Maculae↗

Trandolaprilat, an angiotensin-converting enzyme inhibitor, is not excreted in bile via an ATP-dependent active transporter (cMOAT).

Trandolapril is the prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It has been proposed that its active metabolite, trandolaprilat, is mainly excreted in bile, but this has not been clearly demonstrated. Recently it has been reported that temocaprilat, an active metabolite of the ACE inhibitor temocapril, is effectively excreted in bile via an ATP-dependent active transporter (canalicular multispecific organic anion transporter: cMOAT). To investigate whether trandolaprilat has the pharmacological ability to affect the cMOAT system in a manner similar to temocaprilat. The lipophilicity of trandolaprilat and temocaprilat was measured to determine the n-octanol-water partition coefficients. The dose-dependent inhibition of the up-take of [3H]-estradiol-17beta-D-glucuronide and [3H]-2,4-dinitrophenyl-S-glutathione, which are good substrates for cMOAT, in canalicular membrane vesicles (CMVs) prepared from Sprague-Dawley rats was determined in the presence of trandolaprilat and temocaprilat. The partition coefficient of trandolaprilat (log Po/w - 1.1) was about 30 times higher than that of temocaprilat (log Po/w - 2.5). The uptake of [3H]-estradiol-17beta-D-glucuronide and [3H]-2,4-dinitrophenyl-S-glutathione was dose-dependently inhibited by the presence of temocaprilat, but trandolaprilat had no effect on the transport of [3H]-estradiol-17beta-D-glucuronide or [3H]-2,4-dinitrophenyl-S-glutathione into CMVs even at concentrations as high as 200 microM. It could be concluded that trandolaprilat has a higher lipophilicity than temocaprilat. But the hepatobiliary excretion system via cMOAT may not contribute to the excretion of trandolaprilat in bile.

Adenosine Triphosphate↗

Organized chronic subdural hematoma requiring craniotomy--five case reports.

Two child and three elderly patients underwent craniotomy for organized and/or partially calcified chronic subdural hematomas (CSHs). The characteristic feature of magnetic resonance imaging was a heterogeneous web-like structure in the hematoma cavity. Both children had undergone one side subduroperitoneal shunt for bilateral CSHs when infants. As a result, the opposite hematoma cavities persisted and developed into calcified CSHs after a couple of years. All three elderly patients with senile brain atrophy showed various systemic complications such as cerebral infarction, diabetes mellitus, leg ulceration, cirrhosis, and bleeding tendency. Craniotomy for removal of the hematoma and calcification achieved good results in all patients. Subdural space created by shunt, craniotomy, or brain atrophy and persisting for a certain period, and additional various brain damage such as microcirculatory disorder, meningitis, encephalitis, or premature delivery may be important in generating calcified or organized CSH.

Aged↗

Participation of thrombospondin-1 in the activation of latent transforming growth factor-beta in malignant glioma cells.

Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) and can activate latent TGF-beta. However, the mechanism of the latent TGF-beta activation has not yet been determined. This study examined whether thrombospondin-1 (TSP-1) secreted by malignant glioma cell lines participates in the activation of latent TGF-beta secreted by the glioma cells. Western blot analysis revealed that TSP-1 was present in both the cell lysates and the culture supernatants of all three malignant glioma cell lines (T98G, A172, and U251). A bioassay for TGF-beta activity revealed that all malignant glioma cell lines used in this study could activate latent TGF-beta by themselves. Latent TGF-beta 1 activation, evaluated by enzyme-linked immunosorbent assay, was inhibited by more than 50% by the addition of neutralizing anti-TSP-1 monoclonal antibody or anti-TSP-1 polyclonal antibody. These results indicate that TSP-1 has a predominant role in the activation of latent TGF-beta in malignant glioma cells.

Biomarkers, Tumor↗

[Right ventricular outflow tract reconstruction with PTFE mono-cusped transannular patch for tetralogy of Fallot].

Conotruncal repair for tetralogy of Fallot consists of (1) precise closure of the VSD with the membranous flap and (2) reconstruction of the right ventricular outflow tract (RVOT) by a short transannular patch (< 30% of the RV length) with a wide PTFE monocusp. This report describes the mid-term results in 46 patients with tetralogy of Fallot who underwent conotruncal repair with PTFE monocusped transannular patch and have been followed up for 4 years or more. There was no early and late death and no patient required reoperation. No patient has had a significant residual defect or tricuspid regurgitation (> II). The right and left ventricular pressure ratio was 0.41 +/- 0.12 and the pressure gradient across RVOT was 10.5 +/- 5.9 mmHg, signifying sufficient relief of RVOT obstruction. The mobility of the PTFE monocusp was echocardiographically detected in 86% over a mean follow-up period of 84 +/- 34 months and % freedom from pulmonary regurgitation (> II) was 85.9% at 10 years postoperatively. Excellent long-term durability of the PTFE monocusp provided the normal right vent performance with RVEDV of 91.8 +/- 29.5% of normal and a central venous pressure of 5 +/- 1 mmHg. In conclusion, conotruncal repair with a wide and short transannular patch has provided good mid-term results with the excellent long-term durability of PTFE monocusp.

Adolescent↗

[An epithelial cyst at the frontal convexity].

We report a rare case of an epithelial cyst at the right frontal convexity. A 60-year-old woman came to our hospital suffering from dysarthria and gait disturbance. Computed tomography (CT) of the brain on admission showed a round low-density area, 6 cm in diameter, at the right frontal convexity. Midline shift and displacement of the lateral ventricle are seen. There is no contrast enhancement effect. Excision of the cyst wall and fenestration into the subarachnoid space was carried out and the patient was discharged with no neurological deficits. After 5 years, regrowth of the cyst was seen. Cyst-peritoneal shunt was performed and she was discharged uneventfully. Light microscopy showed the cyst wall consisted of a monolayer of flat epithelium and loose connective tissue. An electronmicrograph of the cyst wall showed a non-ciliated epithelial layer with microvilli and basement membrane. The epithelial cells connecting with each other through desmosome have numerous endoplasmic reticulum and mitochondria. Interdigitation of the cytoplasmic membrane was not seen. The term "epithelial cyst" seems ambiguous. We discuss the pathogenesis and the nomenclature for intracranial benign cystic lesions based on the previous literature.

Arachnoid Cysts↗

Enhancing effect of electric stimulation on cytotoxicity of anticancer agents against rat and human glioma cells.

Electropermeabilization, or electroporation, has been used to deliver genes or drugs into the cytoplasm through micropores in the cell membrane caused by electric stimulation. The cytotoxic effect of a combination of anticancer agents with electric stimulation on rat C6 and human T98G glioma cells was examined in vitro. Electric pulses of 100 microsec square waves (eight cycles at 1 Hz) at various electric fields were delivered to C6 or T98G glioma cell suspensions in combination with several anticancer agents. Cell growth was evaluated 48-72 h after treatment. Measurement of cell lysis by electric stimulation was used to assess the optimum field strength for electroporation. Electric stimulation enhanced significantly the cytotoxicity of bleomycin to both C6 and T98G cells by more than 1000-fold using an electric field of 1750 V/cm for C6 cells and 1000 V/cm for T98G cells. The enhancement disappeared when bleomycin concentration was reduced to 100 pg/ml. The cytotoxicity of carboplatin was weakly but significantly enhanced by electric stimulation when a high dose of carboplatin was used. However, there was no enhancement of the cytotoxicity of nimustine hydrochloride (ACNU), etoposide, and vincristine. These results indicate that the combination of bleomycin and electroporation is the most potent candidate for electrochemotherapy in vivo.

Animals↗

Antiplatelet and antithrombotic effects of orbofiban, a new orally active GPIIb/IIIa antagonist, in guinea pigs.

Antiplatelet and antithrombotic effects of orbofiban, a new orally active glycoprotein IIb/IIIa antagonist, were evaluated in guinea pigs. SC-57101A (0.03-1 microM), the hydrochloride salt of the active form of orbofiban, inhibited in vitro ADP- and collagen-induced platelet aggregation in a concentration-dependent manner. Oral administration of orbofiban (3-30 mg/kg) resulted in dose-dependent inhibition of ADP- and collagen-induced platelet aggregation. The inhibition peaked at 1-2 hours postdose and then declined slowly. The agent also showed similar inhibition of platelet aggregation in guinea pigs with dietary-induced hypercholesterolemia. In contrast, the antiaggregatory effects of acetylsalicylic acid differed more widely between normal and hyperlipidemic animals compared to those of orbofiban. Plasma concentration of the active form, measured by a column-switching HPLC method, correlated well with the inhibition of platelet aggregation. Orbofiban (3-100 mg/kg, p.o.) caused dose-dependent inhibition of thrombus formation in an arteriovenous-shunt-thrombosis model. Orbofiban at high doses (> or =30 mg/kg) and acetylsalicylic acid (100 mg/kg) both prolonged cutaneous bleeding time measured by the template method. These results demonstrate that orbofiban is an orally active and potent inhibitor of platelet aggregation with an efficacy that correlates well with the plasma concentration of its active form.

Adenosine Diphosphate↗

Congenital absence of the horizontal portion of the left portal vein: ultrasound findings.

Congenital absence of the horizontal portion of the left portal vein is very rare and has been very reported sporadically. We present three such cases referred from other hospitals with a diagnosis of intrahepatic vascular anomaly. Color Doppler ultrasound not only confirmed the diagnosis but also allowed a quantitative measurement of blood flow in these cases. Although it is a very rare condition, knowledge of the ultrasound and color Doppler findings helps in establishing the diagnosis of this congenital anomaly.

Congenital Abnormalities↗

Long-standing painless intussusception in adults.

Long-standing painless intussusception in adults is considered to be rare. We report three such cases with an emphasis on color Doppler results. In our three cases the indication for abdominal US was a palpable mass in all these cases, and intussusception was detected by US at a time when the patients had only very mild abdominal discomfort. Persistence of sufficient blood flow, as was suggested by the color Doppler results, was thought to be the most likely pathomechanism of long-standing painless intussusception. The underlying disease was tuberculosis in two of the three cases. Thus, when encountering patients with painless intussusception, tuberculosis must be kept in mind.

Aged↗

Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature.

This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph(+) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. Leukemia(2000) 14, 169-182.

Aged↗

Correlation of thrombospondin-1 and transforming growth factor-beta expression with malignancy of glioma.

The expression of thrombospondin-1 (TSP-1) and its role in gliomas have not been well examined. In the present study TSP-1 expression in a panel of malignant glioma cell lines and the expression of TSP-1 and transforming growth factor (TGF-beta) proteins in low-grade and malignant glioma tissues were investigated. Reverse transcription-polymerase chain reaction analysis showed that nine of nine malignant glioma cell lines expressed TSP-1 mRNA, and seven of nine glioma lines expressed TSP-2 mRNA. Production and secretion of TSP-1 were examined in the T98G glioblastoma cell line by western blot analysis. Total TSP-1 protein content in the supernatant was 10 times higher than that in the cell lysate. Secretion of TSP-1 was examined in these glioma cell lines by western blot analysis. All glioma lines secreted significant levels of TSP-1. Bioassay showed that all tumor lines had the capacity to activate latent TGF-beta. Localization of TSP-1, TGF-beta1, -beta2, and -beta3 was examined immunohistochemically in surgically resected glioma tissues, including 11 glioblastomas, six anaplastic astrocytomas, and eight astrocytomas. Most glioblastomas expressed high levels of both TSP-1 and TGF-beta. Anaplastic astrocytomas expressed moderate levels of TSP-1 and TGF-beta. Most malignant gliomas expressed various levels of TGF-beta1, -beta2, and -beta3. The expression of both proteins, however, was weak in low-grade gliomas. Normal brain tissues around the tumors were negatively or very weakly positively stained for TSP-1 and TGF-beta. These results indicate that most malignant glioma cells express TSP-1 in vitro and in vivo, and the expression of TSP-1 and TGF-beta in vivo correlates with the histologic malignancy of glioma. Overexpression of both TSP-1 and TGF-beta may increase the biologic malignancy of malignant gliomas, through generating the active form of TGF-beta in tumor tissues.

Astrocytoma↗